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Moonlighting of Hae...
Moonlighting of Haemophilus influenzae heme acquisition systems contributes to the host airway-pathogen interplay in a coordinated manner
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- Rodríguez-Arce, Irene (author)
- Institute of Agrobiotechnology (IDAB)
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- Al-Jubair, Tamim (author)
- Lund University,Lunds universitet,Klinisk mikrobiologi, Malmö,Forskargrupper vid Lunds universitet,Clinical Microbiology, Malmö,Lund University Research Groups,University of Copenhagen
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- Euba, Begoña (author)
- CIBER Enfermedades Respiratorias (CIBERES),Institute of Agrobiotechnology (IDAB)
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- Fernández-Calvet, Ariadna (author)
- Institute of Agrobiotechnology (IDAB)
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- Gil-Campillo, Celia (author)
- Institute of Agrobiotechnology (IDAB)
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- Martí, Sara (author)
- CIBER Enfermedades Respiratorias (CIBERES),Bellvitge University Hospital-IDIBELL,University of Barcelona
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- Törnroth-Horsefield, Susanna (author)
- Lund University,Lunds universitet,Biokemi och Strukturbiologi,Centrum för Molekylär Proteinvetenskap,Kemiska institutionen,Institutioner vid LTH,Lunds Tekniska Högskola,Biochemistry and Structural Biology,Center for Molecular Protein Science,Department of Chemistry,Departments at LTH,Faculty of Engineering, LTH
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- Riesbeck, Kristian (author)
- Lund University,Lunds universitet,Klinisk mikrobiologi, Malmö,Forskargrupper vid Lunds universitet,Clinical Microbiology, Malmö,Lund University Research Groups
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- Garmendia, Junkal (author)
- Institute of Agrobiotechnology (IDAB),CIBER Enfermedades Respiratorias (CIBERES)
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(creator_code:org_t)
- 2019-04-11
- 2019
- English 19 s.
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In: Virulence. - : Informa UK Limited. - 2150-5608 .- 2150-5594. ; 10:1, s. 315-333
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Abstract
Subject headings
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- Nutrient iron sequestration is the most significant form of nutritional immunity and causes bacterial pathogens to evolve strategies of host iron scavenging. Cigarette smoking contains iron particulates altering lung and systemic iron homeostasis, which may enhance colonization in the lungs of patients suffering chronic obstructive pulmonary disease (COPD) by opportunistic pathogens such as nontypeable. NTHi is a heme auxotroph, and the NTHi genome contains multiple heme acquisition systems whose role in pulmonary infection requires a global understanding. In this study, we determined the relative contribution to NTHi airway infection of the four heme-acquisition systems HxuCBA, PE, SapABCDFZ, and HbpA-DppBCDF that are located at the bacterial outer membrane or the periplasm. Our computational studies provided plausible 3D models for HbpA, SapA, PE, and HxuA interactions with heme. Generation and characterization of single mutants in the hxuCBA, hpe, sapA, and hbpA genes provided evidence for participation in heme binding-storage and inter-bacterial donation. The hxuA, sapA, hbpA, and hpe genes showed differential expression and responded to heme. Moreover, HxuCBA, PE, SapABCDFZ, and HbpA-DppBCDF presented moonlighting properties related to resistance to antimicrobial peptides or glutathione import, together likely contributing to the NTHi-host airway interplay, as observed upon cultured airway epithelia and in vivo lung infection. The observed multi-functionality was shown to be system-specific, thus limiting redundancy. Together, we provide evidence for heme uptake systems as bacterial factors that act in a coordinated and multi-functional manner to subvert nutritional- and other sources of host innate immunity during NTHi airway infection.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Infektionsmedicin (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Infectious Medicine (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Lungmedicin och allergi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Respiratory Medicine and Allergy (hsv//eng)
Keyword
- heme binding
- iron nutritional immunity
- protein moonlighting
- respiratory infection
Publication and Content Type
- art (subject category)
- ref (subject category)
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